Sustained release of antiinfectives

Abstract

Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.

1 - 92 . (canceled) 
     
     
         93 . A method of treating a mycobacterial pulmonary infection in a patient in need thereof, comprising,
 nebulizing a therapeutically effective amount of a liposomal aminoglycoside composition comprising amikacin, or a pharmaceutically acceptable salt thereof, encapsulated in a liposome having a lipid bilayer comprising a neutral phospholipid and cholesterol, wherein the weight ratio of lipid to the aminoglycoside, or the pharmaceutically acceptable salt thereof, in the composition is 0.75:1 or less, to form a nebulized spray, and   administering the nebulized spray to the patient.   
     
     
         94 . The method of  claim 93 , wherein the amikacin, or pharmaceutically acceptable salt thereof is amikacin sulfate. 
     
     
         95 . The method of  claim 93 , wherein the neutral phospholipid is a phosphatidylcholine. 
     
     
         96 . The method of  claim 94 , wherein the neutral phospholipid is a phosphatidylcholine. 
     
     
         97 . The method of  claim 95 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC). 
     
     
         98 . The method of  claim 96 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC). 
     
     
         99 . The method of  claim 93 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         100 . The method of  claim 94 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         101 . The method of  claim 95 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         102 . The method of  claim 96 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         103 . The method of  claim 97 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         104 . The method of  claim 98 , wherein the mycobacterial infection is  Mycobacterium tuberculosis, Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ),  Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans , or  Mycobacterium fortuitum  complex ( M. fortuitum  and  M. chelonae ). 
     
     
         105 . The method of  claim 99 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         106 . The method of  claim 100 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         107 . The method of  claim 101 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         108 . The method of  claim 102 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         109 . The method of  claim 103 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         110 . The method of  claim 104 , wherein the mycobacterial infection is  Mycobacterium avium  complex (MAC) ( Mycobacterium avium  and  Mycobacterium intracellulare ). 
     
     
         111 . The method of  claim 93 , wherein the liposome has a mean diameter of about 1 um to about 1.0 um. 
     
     
         112 . The method of  claim 111 , wherein the liposome has a mean diameter of about 0.2 μm to about 0.5 μm.